Background: Preserving woman's health and energy level after chemotherapy is an important role for oncology nurses. Non-pharmacological Management of fatigue and other associated symptoms of chemotherapy is very necessary to decrease burden of medication used. Aim: Current study aimed to evaluate the effect of relaxation breathing exercises on fatigue for women with gynecological cancer receiving chemotherapy. Design: A randomized control trial was used. Setting: Current study was carried out at the gynecological ward at nuclear medicine in Mansoura university hospitals, Mansoura city, Egypt. Subjects: One hundred and eighty-three women with gynecological cancer were included. Sample type: Simple random sample was applied.Data collection included three tools which were structured interview questionnaire, piper fatigue scale and women's dairy notes. Results: There was a highly significant difference in fatigue scores between intervention and control. Also, there was a highly statistically significant reduction in fatigue scores between two times RBE and four time's group. As well as, there was a highly significance difference concerning four fatigue domains between intervention and control groups. Moreover, there was a significant difference of mean fatigue score concerning daily activities on the seventh day of the study among intervention (two times group), while, highly significance difference among four times groups and control group. Conclusion: Relaxation breathing exercise is cost effective; non-invasive, easy and safe practice to alleviate cancer related-fatigue especially when conducted four times daily. Moreover, relaxation breathing exercise has a positive effect in improving performance of daily activities and associated symptoms of chemotherapy. Recommendations: Relaxation breathing exercises should be used as the preferred standard procedures after chemotherapy administration.